Tyrosine-based Signals Regulate the assembly of Daple?PARD3 Complex at Cell-cell Junctions during Polarized Planar Cell Migration
Tyrosine-based Signals Regulate the assembly of Daple?PARD3 Complex at Cell-cell Junctions during Polarized Planar Cell Migration
Summary Polarized distribution of organelles and molecules inside a cell is vital for a range of cellular processes and its loss is frequently encountered in disease. Polarization during planar cell migration is a special condition in which cellular orientation is triggered by cell-cell contact. Here, we demonstrate that the multi-modular signaling scaffold Daple (CCDC88C) is a component of cell junctions in epithelial cells which serves like a cellular ‘compass’ for establishing and maintaining contact-triggered planar polarity via its interaction with the polarity regulator PARD3, which has been implicated in both apical-basal and planar polarity. This interaction, mediated by Daple’s PDZ-binding motif (PBM) and the third PDZ domain of PARD3, is fine-tuned by two tyrosine phosphoevents on Daple’s PBM that are known to be triggered by a multitude of receptor and non-receptor tyrosine kinases, such as Src. Hypophosphorylation strengthens the interaction, whereas hyperphosphorylation disrupts it. These findings reveal an unexpected role of Daple within the planar cell polarity pathway as a platform for signal integration and gradient sensing for tyrosine-based signals.
Ear Jason、Saklecha Anokhi、Choi Julie、Kufareva Irina、Ghosh Pradipta、Ghassemian Majid、Rajapakse Navin
Department of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San Diego||Department of Medicine, University of California San Diego||Rebecca and John Moore Comprehensive Cancer Center, University of California San Diego||Veterans Affairs Medical CenterDepartment of Chemistry and Biochemistry, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San Diego
细胞生物学分子生物学生物化学
Ear Jason,Saklecha Anokhi,Choi Julie,Kufareva Irina,Ghosh Pradipta,Ghassemian Majid,Rajapakse Navin.Tyrosine-based Signals Regulate the assembly of Daple?PARD3 Complex at Cell-cell Junctions during Polarized Planar Cell Migration[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/717041.点此复制
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